Jacob Eifer Møller

Jacob Eifer Møller says: “In Denmark, almost 10.000 individuals annually suffer from a heart attack. In 5-10% of the patients, the damage to the heart is so extensive that the heart will not pump enough blood to meet the body’s requirement for oxygen and shock will develop. This condition is called cardiogenic shock. It seems intuitive beneficial to place a device that can pump blood to failing organs when the heart cannot. However, this treatment called mechanical circulatory support (MCS) is costly and associated with risk of serious complications, and evidence to guide choice of treatment is poor. The main objectives of this study are to improve the understanding of the use and consequence of advanced MCS, to improve patient selection for MCS and to assess the most beneficial way to apply this hyperinvasive treatment. This will be pursued through translational research, retrospective data studies with individual validation of data, and through a randomized clinical study.”

Jacob Eifer Møller is Professor at Department of Cardiology Odense University Hospital and University of Southern Denmark and Consultant at the Heart Center, Cardiac Intensive Care Unit, Rigshospitalet.

Vibeke Hjortdal

Vibeke Hjortdal says: “Congenital Heart Diseases are treated with good short-term outcome. Unfortunately, serious complications are seen when they get older. Fluid is filtered out of the blood circulation for the exchange of nutrients and waste products in the microcirculation. Lymphatic vessels transport 8 l of fluid back to the blood every day. Dysfunction results in fluid accumulation as seen in heart failure and edema and protein rich fluid may be lost in the gut or cause breathing problems in the airways. The lives of patients are troublesome and shorter. This project will identify how respiration and exercise can improve the lymphatic function and which medication can improve the lymphatic transport function. The brain is vulnerable in some patients with congenital heart diseases, and they experience psychiatric problems. This project will identify the type of psychiatric problems and in which types of heart diseases the problems are most pronounced and best helped.”

Vibeke Hjortdal is Consultant cardiothoracic surgeon at Department of Cardiothoracic Surgery, Rigshospitalet and Professor at Department of Clinical Medicine, University of Copenhagen.

Rune Hartmann

Rune Hartmann says: Balancing pro-inflammatory and antiviral responses during a viral infection is a key challenge for our immune system and a major determinant of our ability to survive an infection. The pro-inflammatory responses are largely driven by the NFκB signaling pathway but determining the molecular mechanism whereby viral infections induce NFκB signaling and thereby inflammation has proven difficult in mammals. We recently discovered that the STING – NFκB axis represents an evolutionarily conserved antiviral pathway present in all metazoans. In mammals, the NFκB pathway has a dual function and is also required in developmental processes, which makes it difficult to study. In contrast to mammals, flies contain a NFκB transcription factor called Relish, which is required for the immune response, but apparently no function outside immunity. This opens a unique opportunity to use the power of the Drosophila model organism for characterizing the role of the STING – NFκB signaling axis in antiviral immunity and then translate those findings back in the mammalian system. We aim to use the powerful biochemical and genetic tools as well as unbiased screening approaches available in Drosophila to identify key components of the STING – NFκB axis. Our proposed work will allow us to understand how NFκB drives a pro-inflammatory signal and how the resulting inflammation creates significant pathology during viral infection in humans. Knowledge, which may prove critical to develop novel therapeutic strategies for specific targeting of the STING – NFκB signaling axis to lower inflammation in patients.

Rune Hartmann is Professor and Group Leader at the Department of Molecular Biology and Genetics, Aarhus University.

Jakob Nilsson

Jakob Nilsson says: Human health depends on our cells’ ability to respond to changes in the environment and the ability of cells to communicate within and with each other. Such cell signaling and communication depend on a chemical process whereby enzymes add or remove a so-called phosphate group from a protein. Thus, addition and removal of phosphate groups from proteins are fundamental signaling mechanisms that are often deregulated in human disease.  Understanding how the enzymes that add or remove phosphates are regulated will reveal fundamental insight into cell function and will provide a new perspective on human diseases. In this project, we will use new methods we have developed to identify and characterize how the enzymes that remove phosphates are regulated. We will use sophisticated cell biological and biochemical methods to understand how these new regulatory mechanisms impact on cellular function to potentially uncover novel disease-causing mechanisms.

Jakob Nilsson is Professor and Group leader at the Novo Nordisk Foundation Center for Protein Research, University of Copenhagen.

Jørgen Wojtaszewski

This proposal combines in depth investigation of human physiological traits with state-of-art global molecular analyses (omics technology). It concerns aspects to the metabolic action of the hormone insulin, – both when insulin fails to work properly (insulin resistance) and when conditions make insulin work better than normal (insulin sensitization). Our proposal will illuminate molecules that are causing these changes. In this way, we will gain insight to understand insulin resistance – a condition preceding diseases like type 2 diabetes – as well as insight enabling us to enhance insulin sensitivity. We will also explore the value of our analytical platform to be used in stratifying people according to their individual molecular profile (phosphoproteomics) for treatment and prevention strategies – personalized medicine.

Stefano Romeo

Fatty liver disease (FLD) ranges from simple liver fat accumulation to more severe conditions like inflammation, fibrosis and ultimately cirrhosis and cancer. Despite all the efforts, to date there is no approved drug treatment against this disease. Obesity is the strongest environmental risk factor for FLD. However, some individuals, despite being obese, do not have hepatic fat accumulation or, even more surprisingly, although with liver fat, do not progress towards the more severe stages of FLD. Our aim is to understand the protection against FLD and its progression in obese individuals by: A) unravelling the mechanisms behind the beneficial effect of genetic variants protecting against FLD; B) identifying novel protective genetic variants; and C) identifying specific lipid species and metabolic pathways protecting against disease progression. This will finally allow us to identify novel targets and compounds to effectively treat FLD in a framework of precision medicine.

Lars Kai Hansen

Can artificial intelligence algorithms learn to communicate in a language we understand?

Lars Kai Hansen says: “Machine learning algorithms are often perceived as complex black boxes and much research has already gone into opening the black box to explain what has been learned from data. The communication aspects of explainable AI have attracted less attention. The cognitive spaces project is aimed at relating AI explanations better to given user groups and effectively let the algorithms speak the user’s language. We will realize the vision by aligning learned representations of data with formal human knowledge graphs. We hope to understand and push the limits to deep learning interactivity by theoretical and experimental analysis, design of new learning schemes to enable knowledge aware models and explanation.

Our primary use case concerns cognitive spaces for deeper understanding of electric brainwaves (EEG). These signals are of increasing diagnostic importance and EEG signals play a fundamental role in neuroscience. In an ambitious attempt to understand EEG models better we will use cognitive space methods for real-time “captioning” of the brainwave signal”.

Since 2000 Lars Kai Hansen has been a Professor at Technical University of Denmark where he heads the Cognitive Systems group.

Kjeld Schmiegelow

Kjeld Schmiegelow says: “We know of more than 6,000, most often hereditary, “rare diseases” (RD), including childhood cancer. Together, the RD affects more than 250 million people worldwide. In children, cancer is responsible for 20% of all deaths. In PREDICT, we will use cancer in children, and especially leukemia (most common childhood cancer), as a prototype for RD and provide new knowledge about what variations in human genetic material mean for the development of cancer (and other diseases) and for the course of the disease. Using modern genetic engineering, including a new method of analysis that we have developed, we will (i) identify individuals who have a congenital increased risk of developing cancer, (ii) identify whether the new method of analysis can be used in the national screening of newborns for hereditary diseases, (iii) examine thousands of cancer patients to map the effects of hereditary factors on cure rates and the incidence of side effects, and (iv) uncover how patients and healthy individuals experience the application of the new knowledge about their genes.”

Kjeld Schmiegelow is Consultant at the Juliane Marie Centre, Rigshospitalet, and professor in Pediatrics at Department of Clinical Medicine, Copenhagen University since 2005.

Henning Bundgaard

Henning Bundgaard says: “Certain environmental factors and disorders in the expecting mother are associated with heart defects in the newborn. However, these factors may also be associated with more subtle abnormalities in the newborn heart that may present much later in life. This project will investigate the association between common maternal risk factors (diabetes, thyroid and connective tissue disorders) and more overt modifiable factors (smoking, weight and night-shifts) during pregnancy and the impact on the heart in the newborn and later in childhood, through heart examinations of children at birth and again at 5 and 10 years of age. This project will generate knowledge of which neonatally identified subtle abnormalities may require follow-up or even early intervention. The major expectation is to obtain insight into the effects or contributing factors to subgroups of cardiac disorders seen in adults including coronary artery disease, arrhythmias, heart failure, valve calcification and hypertension.”

Henning Bundgaard is Consultant in cardiology at Department of Cardiology, Rigshospitalet, and has been Professor at Institute for Clinical Medicine, University of Copenhagen, since 2015.

Photo: Rigshospitalet

Eva Hoffmann

Eva Hoffmann says: “Up to one in 20 children are born with congenital disorders that originated in the parents’ sperm or egg. This is much higher than in other organisms and we have long wanted to understand what happens when parents pass on their DNA to their children. Questions such as what makes us different from our parents, how does our DNA change, and what can go wrong. We are now in a position to start addressing these fundamental questions about human genetics. We will generate an atlas of sequences from human eggs, sperm and embryos from earliest stages of development to explore what genetic changes we see and how these processes occur. Some of the processes lead to severe genetic aberrations that result in infertility and pregnancy loss, whereas others sustain development – understanding these features of human genetic variation may provide insight into congenital disorders and their origins.”

Eva Hoffmann is Danish and was in 2015 recruited from UK to University of Copenhagen as Professor at ICMM.